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Gluten Intolerance May Not Exist

In 2011, Peter Gibson, a professor of gastroenterology at Monash University and director of the GI Unit at The Alfred Hospital in Melbourne, Australia, published a study that found gluten, a protein found in grains like wheat, rye, and barley, to cause gastrointestinal distress in patients without celiac disease, an autoimmune disorder unequivocally triggered by gluten. Double-blinded, randomized, and placebo-controlled, the experiment was one of the strongest pieces of evidence to date that non-celiac gluten sensitivity (NCGS), more commonly known as gluten intolerance, is a genuine condition.

By extension, the study also lent credibility to the meteoric rise of the gluten-free diet. Surveys now show that 30% of Americans would like to eat less gluten, and sales of gluten-free products are estimated to hit $15 billion by 2016 — that’s a 50% jump over 2013′s numbers!

But like any meticulous scientist, Gibson wasn’t satisfied with his first study. His research turned up no clues to what actually might be causing subjects’ adverse reactions to gluten. Moreover, there were many more variables to control! What if some hidden confounder was mucking up the results? He resolved to repeat the trial with a level of rigor lacking in most nutritional research. Subjects would be provided with every single meal for the duration of the trial. Any and all potential dietary triggers for gastrointestinal symptoms would be removed, including lactose (from milk products), certain preservatives like benzoates, propionate, sulfites, and nitrites, and fermentable, poorly absorbed short-chain carbohydrates, also known as FODMAPs. And last, but not least, nine days worth of urine and fecal matter would be collected. With this new study, Gibson wasn’t messing around.

Oat grains in their husks (Photo credit: Wikipedia)

37 subjects took part, all confirmed not to have celiac disease but whose gastrointestinal symptoms improved on a gluten-free diet, thus fulfilling the diagnostic criteria for non-celiac gluten sensitivity.** They were first fed a diet low in FODMAPs for two weeks (baseline), then were given one of three diets for a week with either 16 grams per day of added gluten (high-gluten), 2 grams of gluten and 14 grams of whey protein isolate (low-gluten), or 16 grams of whey protein isolate (placebo). Each subject shuffled through every single diet so that they could serve as their own controls, and none ever knew what specific diet he or she was eating. After the main experiment, a second was conducted to ensure that the whey protein placebo was suitable. In this one, 22 of the original subjects shuffled through three different diets — 16 grams of added gluten, 16 grams of added whey protein isolate, or the baseline diet — for three days each.

Analyzing the data, Gibson found that each treatment diet, whether it included gluten or not, prompted subjects to report a worsening of gastrointestinal symptoms to similar degrees. Reported pain, bloating, nausea, and gas all increased over the baseline low-FODMAP diet. Even in the second experiment, when the placebo diet was identical to the baseline diet, subjects reported a worsening of symptoms! The data clearly indicated that a nocebo effect, the same reaction that prompts some people to get sick from wind turbines and wireless signals, was at work here. Patients reported gastrointestinal distress without any apparent physical cause. Gluten wasn’t the culprit; the cause was likely psychological. Participants expected the diets to make them sick, and so they did. The finding led Gibson to the opposite conclusion of his 2011 research:

“In contrast to our first study… we could find absolutely no specific response to gluten.”

Instead, as RCS reported last week, FODMAPS are a far more likely cause of the gastrointestinal problems attributed to gluten intolerance. Jessica Biesiekierski, a gastroenterologist formerly at Monash University and now based out of the Translational Research Center for Gastrointestinal Disorders at the University of Leuven in Belgium,* and lead author of the study alongside Gibson, noted that when participants consumed the baseline low-FODMAP diet, almost all reported that their symptoms improved!

“Reduction of FODMAPs in their diets uniformly reduced gastrointestinal symptoms and fatigue in the run-in period, after which they were minimally symptomatic.”

Coincidentally, some of the largest dietary sources of FODMAPs — specifically bread products — are removed when adopting a gluten-free diet, which could explain why the millions of people worldwide who swear by gluten-free diets feel better after going gluten-free.

“On current evidence the existence of the entity of NCGS remains unsubstantiated,” Biesiekierski noted in a review published in December to the journal Current Allergy and Asthma Reports.

Consider this: no underlying cause for gluten sensitivity has yet been discovered. Moreover, there are a host of triggers for gastrointestinal distress, many of which were not controlled for in previous studies. Generally, non-celiac gluten sensitivity is assumed to be the culprit when celiac disease is ruled out. But that is a “trap,” Biesiekierski says, one which could potentially lead to confirmation bias, thus blinding researchers, doctors, and patients to other possibilities.

Biesiekierski recognizes that gluten may very well be the stomach irritant we’ve been looking for. “There is definitely something going on,” she told RCS, “but true NCGS may only affect a very small number of people and may affect more extraintestinal symptoms than first thought. This will only be confirmed with an understanding of its mechanism.”

Currently, Biesiekierski is focused on maintaining an open mind and refining her experimental methods to determine whether or not non-celiac gluten sensitivity truly exists.

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We are constantly hearing of the magic of a gluten free diet. Dubious Diets are as American as well squishy white Wonder Bread. Relying on fads diets to shed a few pounds have been handed down from gullible generation to gullible generation willing to swallow anything promising a trim figure. So it should come as no surprise that in the late 1930s :”The Bread Diet ” was touted as a healthy sure all way to a slim silhouette http://wp.me/p2qifI-2eM

Have they never seen the research by pediatric gastroenterologist, Alessio Fassano, and his research on zonulin, and the increased production of zonulin in response to gluten (in almost everyone), whereby zonulin weakens the tight junctions between the enterocytes, contributing directly to leaky gut (intestinal permeability), thereby allowing gluten to cross the gut barrier and be exposed to the immune system triggering a greater response to gluten?

Did they also control for casein? I understand casein has similar glue-like molecules. I can attest to having drunk a half liter of lactose-free milk and being extremely ill. I am assuming casein was the culprit.

Good question. They didn’t specifically control for casein, however their second experiment with the baseline diet as the placebo sort of renders that null, seeing as how subjects’ symptoms worsened with no changes to their diet whatsoever.

It would depend on how much te elapsed between the two diets. Gluten intolerance is a very suggestive illness – if you accidentally eat a gluten food you cross your fingers and wait – which provokes anxiety too. They would have to control for any food that has a coagulating effect on other foods, which casein also does.

Interesting. There was a “washout” period between all of the treatment diets where subjects returned to the baseline diet: 2 weeks for the first trial, and 3 days for the second trial, or until all symptoms resolved.

I do not have celiac, but I do have a cardiac reaction to repeated exposure to wheat. We know it’s wheat because I can make my ejection fraction change with the addition or exclusion of wheat. A 6 day stint in the cardiac ward with heart failure at 39 years old was pretty convincing. 5 years later and wheat-free my heart has slowly healed itself and is now considered normal. When I can make my symptoms come and go with 100% wheat, you can’t tell me that non-celiac reactions don’t occur.

A few years ago, I started having weird, messed up symptoms that came seemingly out of nowhere. I would start to get intensely hungry, unable to focus on concentrate on anything, get a horrible headache, and more. Over time, the symptoms got worse, and new symptoms, like intense weakness and depression showed up. I had no idea what was causing these symptoms, and I got tested for diabetes and even went to a neurologist. Nothing.

Researching the symptoms, I discovered “a gluten-free, wheat-free diet helps a surprising number of people” who had one of my symptoms: the severe inability to concentrate. I decided “what the heck” and went a full day without eating anything that had wheat in it, not knowing what gluten was.

No symptoms. I figured I’d found the cause. Later, when I ate a gluten-free cupcake that had been made with regular frosting (only the cupcake base was gluten-free; the frosting was added separately), I had a horrifically strong reaction – I ran to the cupcake box to read the ingredients. “Wheat” was listed nowhere. “Barley” was instead, but I didn’t know it contained gluten at the time.

Anyway, through trial and error, and the occasional mistake with horrible consequences, I discovered that I have an intolerance to gluten that’s as severe (in the sense that a tiny amount is enough to send me into a tailspin of symptoms) as any food allergy. However…. I tested negative for celiac disease. (additional trial and error revealed intolerances to milk (casein) and soy, both of which didn’t constitute a big part of my diet and therefore were harder to track down)

So, what do I take away from that? The fact that I reacted to gluten without knowing the food contained it until later, shows it’s not in my head. I no longer have these awful symptoms, and my health has improved a lot since then (this was years ago). And yet, I’ve had the occasional, rare mistake that would trigger those same symptoms – again, before, not after, realizing that gluten (or milk or soy) was in the food.

So if gluten intolerance doesn’t exist and I don’t have celiac disease specifically, then what am I reacting to? Is it just a coincidence that I don’t react to things that don’t have gluten and I react to things that do even if I had no idea gluten was in them? I don’t believe that at all. I know full well when I’m having a reaction or not, and now that I control my diet strictly, I don’t have them except on rare occasions when I eat or drink something that contains said ingredients (what genius puts malt – which is made from barley and contains gluten – in coconut water?????).

It’s irresponsible to print a story like this without noting that there is nearly zero scientific validity to the conclusion of this paper because only 37 patients participated in the entire study.

Sorry, no matter how good the methodology, that’s not a large enough number of cohorts to make any conclusion whatsoever. It’s possible, for instance, that each participant was mistaken about the cause of dietary discomfort.

It leaves this idea as a hypothesis that needs, not only to be repeated, but repeated with a large number of participants. When only 5% of the public is likely (according to researcher/clinician Alessio Fasano, American’s foremost celiac authority) to have NCGS, it’s not difficult to imagine that even without a course in statistics that it’s possible that none of these people actually had a case of NCGS.

A publication such as Forbes embarrasses itself by not insisting that the author at least discuss these findings with an expert in the field or a scientist who understands how meaningless such a tiny study is in the face of millions of anecdotal testimonies from people whose symptoms have improved on a gluten-free diet.

I have biopsy-confirmed celiac disease, but wreckless articles like this one certainly don’t make it any easier to be taken seriously when asperisions are cast on the greater gluten-free community. Shame on you.

With respect, 37 subjects is a good sample size for an in-depth study of this nature. Moreoever, all of the subjects fit the current diagnostic criteria for NCGS and were thoroughly screened to rule out celiac disease.

Dr. Fasano himself recognizes that there are currently no biomarkers for NCGS. (http://www.celiaccentral.org/non-celiac-gluten-sensitivity/testing-and-diagnosis/)

This study certainly should be repeated, as any scientific study of this nature should.

The scientists who conducted this study are leading experts in the field.

Leading experts in the field of nutrition doesn’t mean anything anymore. Turns out I’ve felt and looked best when I avoid most of what our leading experts recommend as a good diet, and completely went agains the grain, pun intended.

My question is,,are other substances in the foods being examined? I myself discovered that soy (not wheat of any form) causes me problems much like the symptoms being attributed to gluten.No,,I am NOT allergic to it yet it causes me some horrible problems. This article does focus somewhat on ‘breads’.I have found that a large percentage of breads,,heck,,MOST commonly available processed foods contain soy products of some sort.From straight up ‘soy flour’ to soy oil to soy lecithin. Not only have I became a much healthier and happier person since I have eliminated it from my diet I have also seen many other folks lives improved when they quit eating it as well. From false cancer diagnosis to no longer being diabetic to eliminating a need for high blood pressure and cholesterol medication as well as dramatic weight loss along with increases in muscle and bone density. I see it as essentially causing a hormone imbalance that then throws the entire system into disorder along with doing some dastardly things to occur in the intestines. But,,I’m no doctor,,so rather than try to explain it all here I have written a few things about my learning experiences over the past several years that I invite anyone and everyone to read and consider.Especially the author of the above article and the researcher written about. Not being sure if Forbes will allow active links I will offer the locations like this: do not use www.just use royharbin dot cwahi dot net slash soy or visit royharbin dot tripod dot com dot blog. Or simply google Roy L.Harbin. After reading about the soy,,please feel free to click around at either site. the tripod site has some other written works that include a quasi biographical story and a fictional tale (in progress/unedited) that are free to read and cwahi has some artwork of mine. I do include reference material garnered from the internet to provide the basis for the conclusions I have came to.

So it seems if you think you have issues with bread, you probably do but for reasons other than gluten insensitivity? There are so many proscriptions in the diet industry that everything has to be viewed skeptically.

Bad science is bad science, and the study you are reporting IS BAD SCIENCE – and, YOU should know it. It is NOT a rigorous study for one simple and obvious reason – the chosen study group! They are “self-reported” gluten sensitive. Ridiculous. Would you do a cholesterol study on self-reported CVD patients? Of course not. That too would be ridiculous. Maybe “Real Clear Science” should be re-labeled Real CRAPPY Science.

All of the subjects in the trial fulfilled the diagnostic criteria for NGCS: They had Celiac disease excluded, but self-reported that their symptoms were controlled by going gluten-free.

Direct quote from the study: “In order to participate in the study, the patients were carefully selected to fulfill current criteria for NCGS.”

Reference:

“Non-celiac gluten sensitivity is diagnosed by process of exclusion. Experts recommend that you first get tested for a wheat allergy and for celiac disease. If both of those are negative, then your doctor may recommend a gluten elimination diet. If symptoms improve on a gluten-free diet, then you likely have non-celiac gluten sensitivity.”

A Gluten Sensitivity identified by HLA-DQB1 602, 0301 not by a process of exclusion. I read the article at Celiac Central. Your article would suggest to me that there is good reason to continue research in this area.

With so many people hearing about gluten — whether they need to avoid it or not — it’s important for people to get the right info. Here’s a great resource for those wanting to know about gluten and gluten-free diets.

I have come to the conclusion that any gastrointestinal distress that I experience is from GMO products. My body does not react to some gluten products but is activated by others. It is almost impossible to track GMOs, but I believe my bodily reaction is a sure indication that GMOs are present.

One problem with this very interesting study is that gluten-intolerant individuals who have a strong reaction to gluten would never volunteer to participate in a study that might expose them to gluten. I fit the description of the subjects in this study, yet no amount of interest, money, or what have you would make it worth participating, due to the pain and suffering I endure after exposure to gluten. So, my interpretation of these findings is that they only apply to individuals who either don’t really have gluten sensitivity, or their reactions are so light that they’d be willing to join the study.

Great point. I’d like to add to that a couple of more points. Someone who is or feels that they are gluten-intolerant would not be eating any gluten and so would not register on any tests for celiac disease. I am not a doctor, but this is based on my discussions and tests that I did with my doctor. From what I understand, you have to have been eating gluten for the celiac test results to be positive.

Furthermore, my experience is that 2 weeks is not nearly long enough of a flush-out time. When my symptoms appeared, it took about 2 months for them to clear completely. Eating gluten can result in damage to the intestines, and that takes a while to heal.

And I agree that no amount of money or interest would have me participate in this study either. I’ve already gone through it and I have no desire to revisit the symptoms. Some of the damage can be permanent, and gastroenterologists are not interested in this problem anyway so why injure myself to contribute to their studies? I went through two of them before I went to a naturopath. All the gastroenterologists want to do is put you on $400/month prescriptions such as asacol. They have no interest whatsoever in finding out what is really ailing you. Guess what? Avoiding gluten is a lot better than taking 6 pills per day and hoping that I never lose my prescription health coverage while taking a chronic and expensive prescription.

I avoid gluten, I quit taking the pills, and I don’t have symptoms anymore. Symptoms that were backed up by the gastroenterologist’s colonoscopy exam and my chronic and sometimes bloody diarrhea. So yeah, they were real.

I find the title misleading. If FODMAPS are the big issue, and bread/wheat, rye, barley, etc are all FODMAPS, wouldn’t it be less of a link bait and more accurate to say “Gluten may not be the only problem”? Due to the type of hypothyroidism I have, it was suggested to me that I remove gluten from my diet. I have come up against a great deal of nay-saying and resistance in attempting to eat gluten-free. Articles with titles like this one only serve to further support people who think I’m full of nonsense for trying to adjust my diet and live a healthier life. In fact, the only reason I came across your article is that smug friends and family read the headline and sent it to me so they could prove their point that I shouldn’t worry about gluten.

This article was recently linked to in a closed forum in which I participate. I noticed that the comments fell into three groups: people with NCGS declaring “but something is making me ill”; people who felt that their suspicions that the sufferers had just been making it up had now been confirmed; and self-proclaimed science types making fun of the ignorance of the masses. I realize that someone who deliberately wants to misinterpret something will do so no matter what, but I feel that the structure of your article may be contributing to the misunderstanding. The title claims NCGS may not exist instead of stating that what we now identify as NCGS may actually be caused by other substances. Likewise, the first half of your article involves a build-up that the researcher who originally provided convincing evidence for NCGS has now debunked it and NCGS may all be in sufferers’ heads — and this was the take-home message for many people on the forum I referred to. While you do later go on to explain the possible role of FODMAPs — and also list it among the possible confounding variables earlier in the article — I do not understand why the reveal seems to be prolonged to create a “twist” in the narrative.

I would like to add that as a gluten intolerant person whey protein can also tear me apart. I have purchased protein powders with whey and have been sick as a dog afterwards. So, using whey as a substitute protein was perhaps a bad idea and could mess with the results.

Thank you Pomeroy for your good summary of Gibsons reports. Unfortunately, this unscientific “researcher” used the number one most commonly intolerated food as his placebo: milk protein. Common lactose intolerance is a totally different thing and the guy apparently has this confused with milk protein reactions — that which is super common in babies but found in plenty of adults as well. The “baseline” diets would have milk too, generally. This non-science makes his “nocebo” comments illegitimate here, though I’m sure it exists (which makes it great to use biopsies, inflammatory markers, and various immune cell and cytokine measurements, and comparing to a legitimate placebo, to see when reactions are actually happening). Milk protein reactions often present the same kind of damage, as seen under the microscope, as that typically described for celiac. Celiac is only one kind of immune reaction to foods. It became a medically recognized distinct entity when very early tests were designed to find some very distinct gluten antibodies. Then anyone who didn’t show these antibodies (or else IgE antibodies to certain foods) was just a psycho case. Today there are at least dozens of different kinds of unfavorable reactions known and shown by researchers, to various food antigens, including celiac-type gluten reactions, non-celiac-type gluten reactions, reactions to other proteins in wheat, and many kinds of reactions to any other foods, and non-protein reactions like the FODMAPS. Real food reactions are growing all the time. Studying babies makes this more distinct to measure, as they’re less prone to psychosomatic, their diets are very simple, they react so commonly, they get great rashes that help diagnose without biopsies, and one can use them as a yardstick for the increasing incidence. WHY is it growing?? For one, we’re destroying our microbiomes, but there are other reasons as well.

What about people who don’t have any gastrointestinal symptoms, but who have autoimmune diseases that improve on a gluten free diet? After I got spondyloarthritis in 2010, I tried to eliminate various foods and found out I could cure myself by avoiding gluten and reducing carbs. I went from having difficulties walking to running several times a week, with no medication. I have also read research on how diseases like MS, Schizophrenia, Ankylosing Spondylitis (and other HLA-B27 diseases) ++ can improve with this type of diet. The leaky gut hypothesis should be researched more. And I never buy gluten free (high starch) prodessed products. It is easy to make your own gluten free foods, with lots of vitamins and fiber.

What about people with no gastrointestinal symptoms, but who are cured from various autoimmune or psychiatric diseases by eliminating gluten? When I got spondyloarthritis in 2010 I tried to eliminate various foods, and after a year of testing diets, I found out I could cure myself by avoiding gluten. It was difficult to figure out that gluten caused my symptoms, because I didn’t have any celiac or gastrointestinal symptoms. And here in Norway, I had never heard of the gluten free diet linked to anything but celiac disease at that time. I went from having difficulties walking, to running several times a week now, and I take no medication. I have read that diseases like MS, HLA-B27 diseases (like Anylosing S. ), Schizophrenia etc can improve by eliminating gluten and strenghtening the gut. I also think lacking good bacterias in the gut and eating too much sugar, dairy and processed foods is a factor. Studying nutrition and diseases is not easy, but the leaky gut hypothesis should be researched more.

As anyone who has done anything north of a high school science project will tell you, a study with 37 people in it isn’t even remotely scientifically applicable to anything. And without even looking I can assure you that the study was funded by the The Grain Foods Foundation or the Whole Grain Council.

Gluten intolerance is a real illness with many ACTUALLY VIABLE scientific studies, and our modern wheat DOES contain many times the gluten content that wheat used to have. Its also worth noting that many grains and seeds have high gluten and phytic acid content to allow the grain/seed to pass through the digestive tract and remain viable as a seed when excreted to help spread the seed. These are ‘foods’ designed to foil digestion and when it is digested, is converted almost entirely to sugar in the blood stream. Diabetes anyone? Sugar rollercoaster perhaps? If eating a lot of this seems like a good idea, think again.

As someone who is Gluten intolerant and uses a Gluten Free diet to control my Chron’s disease, I am very interested in this topic. My wife did some research while in her PhD program and found (other research) that indicated the area of the world in which you come from has a strong influence on what can irritate you too. Only way to find out what impacts you is an elimination diet which most of us don’t have the discipline to complete.

I don’t see it discussed in the full text… the “baseline” diet was, I assume, just their usual normal diet (which would have included milk and gluten)? The paper also does not mention that whey was used as the “placebo” — such an unfortunate move. I really appreciate your article that brings up this factor. It’s well known that milk protein intolerance is frequent with gluten intolerance.